Advertisement

Oral Agents for Type-2 Diabetes

  • Ronald A. Codario
Chapter
Part of the Current Clinical Practice book series (CCP)

Abstract

Clearly oral agents are more popular with patients in the battle for glycemic control. Significant recent advances in oral agents have provided several interesting and synergistic medications to make glycemic control more attainable. These newer agents, by addressing the various causes of hyperglycemia in the type-2 diabetic state can be used synergistically with enhanced glycemic control.

Key words

Oral agent classes Oral agent combinations Multiple oral agent therapy, Hyperglycemia Glycogenolysis Gluconeogenesis 

References

  1. 1.
    Hurst RT, Lee RW. Increased incidence of coronary atherosclerosis in type-2 diabetes mellitus: mechanism and management. Ann Intern Med 2003;139(10):824–834.PubMedCrossRefGoogle Scholar
  2. 2.
    Wallace TM, Matthews DR. Poor glycemic control in type-2 diabetes. QJM 2000;93(6):369–374.PubMedCrossRefGoogle Scholar
  3. 3.
    Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: the glitazones or insulin sensitizers. Annu Rev Med 2001;173:54–57.Google Scholar
  4. 4.
    Luna B, Feinglos MN. Oral agents in the management of type-2 diabetes mellitus. Am Fam Physician 2001;63:1747–1756.PubMedGoogle Scholar
  5. 5.
    Feinglos FM, Bethel MA. Therapy of type-2 diabetes, cardiovascular death and the UGDP. Am Heart J 1999;138:S346–S352.PubMedGoogle Scholar
  6. 6.
    Sutton MS, Rendell M, Randona P. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type-2 diabetes. Diabetes Care 2002;25(11):2058–2064.CrossRefGoogle Scholar
  7. 7.
    Simpson SH, Majumdar SR, Tsuyuki RT. Metformin reduces cardiovascular mortality risks vs. placebo and other oral diabetes drugs in type-2 diabetes. N Engl J Med 2007;356:2457–2471.CrossRefGoogle Scholar
  8. 8.
    Rao A, Kuhadiya N, Reynolds, K, Fonseca V. Is the combination of metformin and a sulfonylurea associated with increased risk of cardiovascular disease and all cause mortality? Diabetes Care 2008;31(8):1672–1678.PubMedCrossRefGoogle Scholar
  9. 9.
    Ahmann AJ, Riddle MC. Oral pharmacological agents. In: Medical Management of Diabetes Mellitus. New York, NY: Marcel Decker, CRC press 2000;267–283.Google Scholar
  10. 10.
    DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999;131:281–303.PubMedCrossRefGoogle Scholar
  11. 11.
    Malmberg K, Ryden L, Efendic S. Randomized trial of insulin glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study). J Am Coll Cardiol 1995;26:57–65.PubMedCrossRefGoogle Scholar
  12. 12.
    Codario R. A guide to combination therapy in type 2 diabetes. Patient Care 2003;37(4):16–24.Google Scholar
  13. 13.
    Dude DS, Peiris AN. Concise update to managing adult diabetes. South Med J 2002;95:4–9.Google Scholar
  14. 14.
    Horton ES, Clinkinbeard C, Gatlin M, et al. Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes. Diabetes Care 2000;23:1660–1665.PubMedCrossRefGoogle Scholar
  15. 15.
    United Kingdom Pospective Diabetes Study Group (UKPDS). Effect of intensive blood glucose control with metformin on complications in overweight patients with type-2 diabetes. Lancet 1998;352:854–865.CrossRefGoogle Scholar
  16. 16.
    Fontbonne A, Charles MA, Juhan-Vague I, Bard MM, Andre P, Isnard F. The effect of metformin on the metabolic abnormalities associated with upper body fat distribution. BIGPRO Study Group. Diabetes Care 1996;19:920–926.PubMedCrossRefGoogle Scholar
  17. 17.
    Reaven GM, Johnston P, Hollenbeck CB, et al. Combined metformin-sulfonylurea treatment of patients with non-insulin dependent diabetes in fair to poor glycemic control. J Clin Endocrinol Metab 1992;74:1020–1026.PubMedCrossRefGoogle Scholar
  18. 18.
    Dailey GE. Improving oral pharmacologic treatment and management of type-2 diabetes. Manag Care 2004;13:41–47.PubMedGoogle Scholar
  19. 19.
    Kuritsky L, Samraj G, et al. Improving management of type 2 diabetes mellitus: alpha glucosidase inhibitors. Hosp Pract 1999;34:43–46.CrossRefGoogle Scholar
  20. 20.
    Parulkar A, Pendergrass M, et al. Non hypoglycemic effects of thiazolidinediones. Ann Intern Med 2001;134:61–71.PubMedCrossRefGoogle Scholar
  21. 21.
    Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure. Diabetes Care 2007;30:2148–2153.PubMedCrossRefGoogle Scholar
  22. 22.
    Malinowski JM, Bolesta S. Rosiglitazone in the treatment of type-2 diabetes mellitus: a critical review. Clin Ther 2000;22:1151–1168.PubMedCrossRefGoogle Scholar
  23. 23.
    Goldberg RB, Kendall DM, Deeg MA, Buse JB, Zagar AJ. A comparison of lipid and glycemic effects of pioglitazone in patients with type-2 diabetes and dyslipidemia. Diabetes Care 2005;28:1547–1554.PubMedCrossRefGoogle Scholar
  24. 24.
    Bell DS, et al. Long term efficacy of triple oral therapy for type 2 diabetes mellitus. Endocr Pract 2002;8:271–275.PubMedCrossRefGoogle Scholar
  25. 25.
    Davidson M, Meyer P, Haffner S, Feinstein S, Kondos G, D’Agostino R. Increases in HDL-C in the CHICAGO Study explain the benefits of pioglitazone for reducing CMT progression in patients with type-2 diabetes. 43rd Annual Meeting of the European Association for the Study of Diabetes, 2007. Abstract 0864.Google Scholar
  26. 26.
    Nissen S, Nicholls S, Wolski K, Nesto R. Comparison of pioglitazone vs. glimepiride on progression of coronary atherosclerosis in patients with type-2 diabetes. JAMA 2008;299(13):1561–1572.PubMedCrossRefGoogle Scholar
  27. 27.
    Dormandy JA, Charbonnel B, Eckland DJA. Secondary prevention of macxrovascular events in patients with type-2 diabetes in the PROactive study. Lancet 2005;366(9493):1279–1289.PubMedCrossRefGoogle Scholar
  28. 28.
    Gerstein HC, Yusuf S, Bosch J. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: the DREAM trial. Lancet 2006;368:1096–1105.PubMedCrossRefGoogle Scholar
  29. 29.
    Ovalle F, Bell DSH. Lipoprotein effects of different thiazolidindiones in clinical practice. Endocr Pract 2002;8:406–410.PubMedCrossRefGoogle Scholar
  30. 30.
    Dormuth C, Carney G, Carleton B. Thiazolidinediones and fractures in men and women. Arch Intern Med 2009;169(15):1395–1402PubMedCrossRefGoogle Scholar
  31. 31.
    Grey A. Skeletal consequences of thiazolidinediones. Osteoporos Int 2008;19(2):129–137.PubMedCrossRefGoogle Scholar
  32. 32.
    Holst JJ, Deacon CF. Glucagon like peptide-1 mediates the therapeutic actions of DPP-4 inhibitors. Diabetologia 2005;48:612–615.PubMedCrossRefGoogle Scholar
  33. 33.
    Drucker DJ. Enhancing incretin action for the treatment of type-2 diabetes. Diabetes Care 2003;26:2929–2940.PubMedCrossRefGoogle Scholar
  34. 34.
    Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type-2 diabetes. Diabetes Care 2006;29:2632–2637.PubMedCrossRefGoogle Scholar
  35. 35.
    Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type-2 diabetes. Diabetes Care 2006;29:2338–2643.CrossRefGoogle Scholar
  36. 36.
    Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. Efficacy and safety of sitagliptin added to ongoing pioglitazone therapy in patients with type-2 diabetes. Clin Ther 2006;28:1556–1568.PubMedCrossRefGoogle Scholar
  37. 37.
    Bosi E, Camisasca RP, Collober C, Rochotte E. Garber AJ. Effects of vildagliptin on glucose control in patients with type-2 diabetes inadequately controlled on metformin. Diabetes Care 2007;30:890–895.PubMedCrossRefGoogle Scholar
  38. 38.
    Feng J, Zhang Z, Wallace MB. Discovery of alogliptin: a potent, selective, bioavailable and efficacious inhibitor of dipeptidyl peptidase IV. J Med Chem 2007;50(10):2297–2300.PubMedCrossRefGoogle Scholar
  39. 39.
    Anduri R, Drincic A, Rendell M. Alogliptin: a new addition to the DPP-IV inhibitors. Diabetes Metab Syndr Obes 2009;2:1–3.Google Scholar
  40. 40.
    Rosenstock J, Rendell M, Gross J. Alogliptin added to insulin therapy in patients with type-2 diabetes reduces A1C without weight gain. Presented at the 68th Session of the ADA, June 6–10, 2008, San Francisco, CA. Abstract 444-P.Google Scholar
  41. 41.
    DeFronzo R, Hissa M, Garber A, Gros JL. The efficacy and safety of saxagliptin when added to metformin therapy in type-2 diabetic patients not adequately controlled on metformin alone. Diabetes Care 2009;32(9):1649–1655.PubMedCrossRefGoogle Scholar
  42. 42.
    Augeri D. Discovery and pre-clinical profile of saxagliptin. J Med Chem 2005;48(15):5025–5037.PubMedCrossRefGoogle Scholar
  43. 43.
    Chiang JY, Kimmel R, Weinberger C, Stroup D. Farnesoid X receptor responds to bile acids and represses cholesterol 7 alpha-hydroxylase gene transcription. J Biol Chem 2000;275:10918–10924.PubMedCrossRefGoogle Scholar
  44. 44.
    Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose lowering effect of WelChol study (GLOWS). Clin Ther 2007;29:74–83.CrossRefGoogle Scholar
  45. 45.
    United Kingdom Prospective Diabetes Study. 13. Relative efficacy of randomly allocated diet, sulfonylurea, insulin or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ 1995;310:83–88.CrossRefGoogle Scholar
  46. 46.
    Mudaliar S, Henry RR. New oral therapies for type-2 diabetes mellitus: the glitazones or insulin sensitizers. Annu Rev Med 2001;52:239–257.PubMedCrossRefGoogle Scholar
  47. 47.
    Fonseca V, Grunberger G, Gupta S. Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control. Diabetes Care 2003;26(6):1685–1690.PubMedCrossRefGoogle Scholar
  48. 48.
    DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin dependent diabetes mellitus. The Mutilcenter Metformin Study Group. N Engl J Med 1995;333:541–549.PubMedCrossRefGoogle Scholar
  49. 49.
    Moses R, et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 1999;22(1):119–124.PubMedCrossRefGoogle Scholar
  50. 50.
    Hanefield M, Bouter KP, et al. Rapid and short acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia. Diabetes Care 2000;23:349–353.CrossRefGoogle Scholar
  51. 51.
    Inzucchi SE. Oral antihyperglycemic therapy for type-2 diabetes. JAMA 2002;287:360–372.PubMedCrossRefGoogle Scholar
  52. 52.
    Rosenstock J, Brown A, Fischer J, Jain A. Efficacy and safety of acarbose in metformin treated patients with type-2 diabetes. Diabetes Care 1998;21(12):2050–2055.PubMedCrossRefGoogle Scholar
  53. 53.
    Miller S, St. Ange E. Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type-2 diabetes. Ann Pharmacother 2006;40(7):1336–1343.PubMedCrossRefGoogle Scholar
  54. 54.
    Bays H, Goldberg R, Truitt K, Jones M. Colesevelam hydrochloride therapy in patients with type-2 diabetes mellitus treated with metformin. Arch Intern Med 2008;168(18):1975–1983.PubMedCrossRefGoogle Scholar

Supplementary Readings

  1. Buse J. Combining insulin and oral agents. Am J Med 2000;108(suppl 6a):23S–32S.PubMedCrossRefGoogle Scholar
  2. Bloomgarten ZT. Gut hormones and related concepts. Diabetes Care 2006;29:2319–2324.CrossRefGoogle Scholar
  3. Dunn CJ, Faulds D. Nateglinide. Drugs 2000;60:607–617.PubMedCrossRefGoogle Scholar
  4. Evans A, Krentz AJ. Benefits and risks of transfer from oral agents to insulin in type 2 diabetes mellitus. Drug Saf 1999;21:7–22.PubMedCrossRefGoogle Scholar
  5. Glucovance (glyburide and metformin HCL tablets) Package Insert. Bristol Myers Squibb Company, Princeton, NJ. July 2000.Google Scholar
  6. Heinemann L. Hyperglycemia and insulin analogues: is there a reduction in the incidence. J Diabetes Complications 1999;13:105–114.PubMedCrossRefGoogle Scholar
  7. Kabadi M, et al. Efficacy of sulfonylureas with insulin in type 2 diabetes mellitus. Ann Pharmacother 2003;37:1572–1576.PubMedCrossRefGoogle Scholar
  8. Kirpichnikov D, et al. Metformin, an update. Ann Intern Med 2002;137:25–33.PubMedCrossRefGoogle Scholar
  9. Kudlacek S, Schernthaner G. The effect of insulin treatment on HbDPP-IV, body weight and lipids in type-2 diabetic patients with secondary failure to sulfonylureas. Horm Metab Res 1992;24:478–483.PubMedCrossRefGoogle Scholar
  10. Motz R. Metformin associated lactic acidosis: fact, fiction or both. CV&R, March–April 2004, 74–75.Google Scholar
  11. Palumbo PJ. Glycemic control, mealtime glucose excursions, and diabetic complications in type 2 diabetes mellitus. Mayo Clin Proc 2001;76:609–618.PubMedGoogle Scholar
  12. Starlix Package Insert. Novartis Pharmaceuticals Corp., Basel, Switzerland. 2001.Google Scholar
  13. Sherwin RS, et al. The prevention or delay of type 2 diabetes. Diabetes Care 2002;25:743.Google Scholar
  14. Unger J. Targeting glycemic control in the primary care setting. Female Patient 2003;28:12–16.Google Scholar
  15. Yki-Jarvinen H, Ryysy L, Nikkila K, et al. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1999;130:389–396.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ronald A. Codario
    • 1
  1. 1.University of Pennsylvania Health System Thomas Jefferson University HospitalPhiladelphiaUSA

Personalised recommendations